Past studies of the pathogenesis of hypoxemia in patients with cardiac or respiratory diseases have stressed anatomical causes, such as defective gas exchange or circulatory shunts. Relatively little attention has been given to the role of deficient hypoxic ventilatory drive. The objectives of the proposed research are to: 1) Ascertain mechanisms by which carotid body response to hypoxia may be altered with special attention being given to the role of the sympathetic nervous system and the possible influence of temperature, 2) evaluate techniques for assessing central respiratory center responsiveness to carotid body excitation and examine conditions under which this can be altered, and 3) determine the roles of the carotid body and arterial carbon dioxide tension in altering the hypoxic ventilatory depression point. Techniques have been developed using an on-line computer to assess the response of both carotid body neural output and minute ventilation to isocapnic hypoxic stimulus. Sympathetic involvement in carotid body control will be determined by stimulating or cutting the sympathetic input as well as by administration of alpha-adrenergic blocking drugs. Central responsiveness to carotid body stimulation and the influence of arterial carbon dioxide tension on ventilatory depression point will be evaluated by cross plots of minute ventilation against chemoreceptor neural output.